Conserved intron positions in ancient protein modules

Background  

The timing of the origin of introns is of crucial importance for an understanding of early genome architecture. The Exon theory of genes proposed a role for introns in the formation of multi-exon proteins by exon shuffling and predicts the presence of conserved splice sites in ancient genes. In this study, large-scale analysis of potential conserved splice sites was performed using an intron-exon database (ExInt) derived from GenBank.     

Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age,Geography, and Lifestyle

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Sepsis progression and outcome: a dynamical model

Background  

Sepsis (bloodstream infection) is the leading cause of death in non-surgical intensive care units. It is diagnosed in 750,000 US patients per annum, and has high mortality. Current understanding of sepsis is predominately observational and correlational, with only a partial and incomplete understanding of the physiological dynamics underlying the syndrome. There exists a need for dynamical models of sepsis progression, based upon basic physiologic principles, which could eventually guide hourly treatment decisions.     

A novel approach for multi-domain and multi-gene family identification provides insights into evolutionary dynamics of disease resistance genes in core eudicot plants

Background

Recent advances in DNA sequencing techniques resulted in more than forty sequenced plant genomes representing a diverse set of taxa of agricultural, energy, medicinal and ecological importance. However, gene family curation is often only inferred from DNA sequence homology and lacks insights into evolutionary processes contributing to gene family dynamics. In a comparative genomics framework, we integrated multiple lines of evidence provided by gene synteny, sequence homology and protein-based Hidden Markov Modelling to extract homologous super-clusters composed of multi-domain resistance (R)-proteins of the NB-LRR type (for NUCLEOTIDE BINDING/LEUCINE-RICH REPEATS), that are involved in plant innate immunity.

Results

To assess the diversity of R-proteins within and between species, we screened twelve eudicot plant genomes including six major crops and found a total of 2,363 NB-LRR genes. Our curated R-proteins set shows a 50% average for tandem duplicates and a 22% fraction of gene copies retained from ancient polyploidy events (ohnologs). We provide evidence for strong positive selection and show significant differences in molecular evolution rates (Ka/Ks-ratio) among tandem- (mean = 1.59), ohnolog (mean = 1.36) and singleton (mean = 1.22) R-gene duplicates. To foster the process of gene-edited plant breeding, we report species-specific presence/absence of all 140 NB-LRR genes present in the model plant Arabidopsis and describe four distinct clusters of NB-LRR “gatekeeper” loci sharing syntenic orthologs across all analyzed genomes.

Conclusion

By curating a near-complete set of multi-domain R-protein clusters in an eudicot-wide scale, our analysis offers significant insight into evolutionary dynamics underlying diversification of the plant innate immune system. Furthermore, our methods provide a blueprint for future efforts to identify and more rapidly clone functional NB-LRR genes from any plant species.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-966) contains supplementary material, which is available to authorized users.     

Microsatellite instability in IVS3 of murine c-fes gene: Tumor-associated rearrangement and mammalian divergence

The murine lymphomacrophage hybrids ESb, EbF₁, EbF_2-c4, which express c-fes constitutively, were found by Southern analysis to bear a c-fes deletion of almost 100 bp. The deleted allele was transmitted to the metastatic hybrids by their nonexpressing, poorly metastatic T-lymphoma progenitor Eb, which also has a structurally normal c-fes allele. PCR amplification and sequencing of fes cDNA spanning exons 3–5, where the deletion mapped, ruled out any involvement of coding sequences in the rearrangement. PCR amplification of the as yet unsequenced murine c-fes IVS3 and IVS4 showed they are about 50% longer than their human and feline homologs. Sequencing of IVS4 showed no difference between tumor and control DNA. Sequencing of part of the ∼2600-bp IVS3 was guided by the restriction analysis of PCR products from control and hybrid DNAs. This showed that differences from the control appeared to be mainly located in the 900-bp HindIII-EcoRI fragment, localized in the middle of IVS3. As all three hybrids had the same restriction map, this fragment was sequenced in one of them (ESb). A run of >200 CA repeats was found in control DNA, and a reduction in the CA_n microsatellite accounted for most of the c-fes deletion in the ESb hybrid. Interestingly, the 50% reduction in the size of human and feline c-fes IVS3 as compared with the murine homolog is mostly due to contraction of the same microsatellite. Received: 6 November 1995 / Accepted: 2 May 1996     

Diet-induced obesity in rats leads to a decrease in sperm motility

Background  

Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters.     

An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome

Rothmund-Thomson syndrome (OMIM #268400) is a severe autosomal recessive genodermatosis: characterised by growth retardation, hyperpigmentation and frequently accompanied by congenital bone defects, brittle hair and hypogonadism. Mutations in helicase RECQ4 gene are responsible for a subset of cases of RTS. Only six mutations have been reported, thus, far and each affecting the coding sequence or the splice junctions. We report the first homozygous mutation in RECQ4 helicase: 2746-2756-delTGGGCTGAGGC in IVS8 responsible for the severe phenotype associated with RTS in a Malaysian pedigree. We report also a 5321 G-->A transition in exon 17 and the updated list of the RECQ4 gene mutations.     

Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus cascavella rattlesnake (Maracambóia) venom

The PLA₂ and crotapotin subunits of crotoxin from Crotalus durissus cascavella venom were purified by a combination of HPLC molecular exclusion (Protein Pack 300SW column) and reverse-phase HPLC (RP-HPLC). Tricine SDS—PAGE showed that the PLA₂ and crotapotins migrated as single bands with estimated molecular masses of 15 and 9 kDa, respectively. The amino acid composition of the PLA₂ showed the presence of 14 half-cysteines and a high content of basic residues (Lys, Arg, His), whereas the crotapotins were rich in hydrophobic, negatively charged residues and half-cysteines. The PLA₂ showed allosteric behavior, with maximal activity at pH 8.3 and 35–40°C. The C. d. cascavella PLA₂ required Ca²⁺ for activity, but was inhibited by Cu²⁺ and Zn²⁺ and by Cu²⁺ and Mg²⁺ in the presence and absence of Ca²⁺, respectively. Crotapotin (F3) and heparin inhibited the catalytic activity of the PLA₂ by acting as allosteric inhibitors.